The hypothesis that the pancreatic beta cell is a primary site of pathology in human diabetes mellitus, and that the number of functioning beta cells may play a role in the initiatian and/or outcome of this disease, has again directed out attention to the need for further study of the embryogenesis and natural history of the beta cell and of the pancreatic islets. This request is for support of several research projects designed to clarify and correlate ultrastructural and functional events within the pancreatic islets of human and subhuman primates, and in laboratory models of drug induced or spontaneous diabetes mellitus. The resolution of controversial concepts of factors which may regulate beta cell genesis and neogenesis has been hindered heretofore by the unavailability of satisfactory model systems for studying pancreatic islet cells in vitro. This request is therefore also for support of projects designed to study and correlate morphologic and functional events within monolayer cultures of pancreatic endocrine cells. The hypothesis that the pancreatic beta cell is a primary site of pathology in genetic human diabetes mellitus and the concept that this defect is characterized by a deficiency of circulating insulin have directed our attention to the need for further studies of insulin secretion. This request is also for support of several research projects designed to clarify morphologic aspects of changing beta cell function in fetal and adult subhuman primates and in laboratory models of spontaneous diabetes mellitus.